Gene expression of neuropeptide Y in the nucleus of the solitary tract is activated in rats under restricted daily feeding but not under 48-h food deprivation

The two neuropeptide Y (NPY) systems innervating the hypothalamic paraventrivular nucleus were examined regarding their roles in the prefeeding corticosterone peak developed under restricted daily feeding (RF). Protein and mRNA levels of NPY were measured in the arcuate nucleus (ARC) and the nucleus of the solitary tract (NST) in rats under 48-h food deprivation (48-hFD), RF, and 72-h food deprivation imposed after RF (post-RF 72-hFD) with 7 days of ad libitum feeding in between. NPY protein and mRNA levels in the ARC significantly increased with 48-hFD and decreased with re-feeding, whereas those in the NST were not changed by 48-hFD. When rats had RF imposed with free access to food from 10.00 to 12.00 h (lights on from 06.00 to 18.00 h) for 3 weeks, NPY concentrations in the ARC increased at 10.00 h, just prior to the daily meal, but those in the NST did not change significantly throughout the period examined. On the other hand, NPY mRNA levels in both the ARC and NST increased before the meal supply and remained high for 4 h after feeding. Under post-RF 72-hFD, the prefeeding peak of NPY mRNA was detected in the NST, but NPY mRNA levels in the ARC were continuously high throughout the 24-h period. These findings indicate that the NPY neurons from the NST are specifically activated by RF, whereas those from the ARC are generally stimulated by an increased food demand.     

Nitric oxide synthase expressions in rat dorsal root ganglion after a hind limb tourniquet

We investigated the mRNA levels of neuronal, inducible, endothelial nitric oxide synthases (nNOS, iNOS, eNOS) and tumor necrosis factor-alpha (TNF-alpha) in a rat dorsal root ganglion (DRG) after tourniquet application to a hind limb to identify molecules that trigger secondary events after peripheral nerve injury. Significantly high nNOS, iNOS mRNA and protein levels were observed in the ipsilateral DRGs 4 h after tourniquet application but not in the contralateral or control DRGs. The levels of TNF-alpha, an inducer of iNOS, were significantly increased in the ipsilateral DRGs 1 h after tourniquet application. Large amounts of NO might result in damage to the host cells and induce apotosis to eliminate damaged cells during the early stage of nerve injury.     

DNA microarray cluster analysis reveals tissue similarity and potential neuron-specific genes expressed in cranial sensory ganglia

Each of four cranial sensory ganglia, trigeminal, geniculate, petrosal, and nodose ganglia, contains multiple kinds of sensory neurons with different cell morphologies and neuronal properties that transmit information about sensory stimuli received peripherally. Here we analyze the complex properties of these neurons from the viewpoint of gene expression using DNA microarrays by cluster analysis. From a total of 8,740 genes, 498 genes were selected as showing tissue-dependent expression on the microarray by hierarchical cluster analysis, and their profiles indicated that, among the four sensory ganglia, the petrosal and trigeminal ganglia are intimately related. Tissue trees of 37 subclusters containing the 498 genes showed that the profiles of gene expression and the subclusters were classified into a smaller number of groups (18 groups) when information on the amounts of expression was added. In situ hybridization analysis of 21 genes selected from 13 different groups was carried out, and the gene expression patterns were classified into eight categories. The putative profiles postulated from the microarray data were essentially consistent with the patterns of expression at the cellular level as shown by in situ hybridization. In conclusion, from the overall analyses of gene expression by DNA microarray, we can identify a number of candidate genes showing neuron type-specific expression in the peripheral ganglia.     

Carbamazepine-induced abnormal pitch perception

A 7-year-old boy began to complain that his pitch perception was decreased just after oral medication with carbamazepine was initiated for the treatment of epilepsy. When he played the piano, he felt as if he had played a musical note of almost a half pitch lower than he had. His pitch perception recovered soon after the cessation of carbamazepine. A 14-year-old girl noted a lowered pitch of music sounds while she played the piano just after the administration of carbamazepine for the treatment of epilepsy. Carbamazepine was withdrawn and the auditory symptoms disappeared. Both patients were musically trained. Reversible pitch perception abnormalities are a rare adverse effect of carbamazepine, however, the clinical features of the reported cases were similar; they were musically trained, young, female and Japanese. Although the mechanism remains unclear, we have to pay attention to this subtle adverse effect when we treat epileptic patients with carbamazepine.     

Nitrazepam for the treatment of Lennox-Gastaut syndrome

Lennox-Gastaut syndrome is a severe childhood epileptic syndrome with encephalopathy and multiple seizure types, which are often intractable to treatment. Most of these children will ultimately become mentally retarded and dependent on others for their daily care. Antiepileptic drugs are the mainstay of treatment, however, no particular drug is entirely effective. Apart from the use of antiepileptic drugs, nonpharmacologic treatments are also considered (i.e., callosotomy, ketogenic diet, and vagus nerve stimulation), which have proven to be partially effective. We prospectively studied 14 children (11 months-8 years of age) with medication-resistant Lennox-Gastaut syndrome, being treated with nitrazepam (open-label compassionate protocol). We compared the 1-month baseline seizure frequency with the median seizure rate reduction during the first 12 months of treatment with nitrazepam. The median seizure rate reduction during the first 12 months of treatment with nitrazepam was 41% (P = 0.001), with more than 50% seizure reduction in 60% of patients. Two patients became seizure free, five patients demonstrated at least 50% reduction in seizure rates, six patients had at least 25% seizure rate reduction, and one patient did not respond. No patient had any serious adverse effects. Side effects included sedation in six children (40%) and drooling in nine patients (60%).     

Long-term audiological feature in Pendred syndrome caused by PDS mutation

Pendred syndrome is an autosomal recessive disorder characterized by profound deafness in childhood and goiter. We report a case of Pendred syndrome in a 27-year-old woman who had a diffuse goiter and progressive sensorineural hearing loss with fluctuation and a missense mutation (His723Arg) in the PDS gene identified in a homozygous state. Audiological findings were observed clinically over a 20-year period. Progressive hearing loss with fluctuation occurred before age 12 years. An enlarged vestibular aqueduct with enlargement of the endolymphatic duct and sac was confirmed with 3-dimensional magnetic resonance imaging hydrography.     

Cell adhesion glycoproteins in the human lamina cribrosa

PURPOSE: The distribution of the cell adhesion glycoproteins, laminin, fibronectin, tenascin, vitronectin, thrombospondin, and entactin/nidogen, was examined in the human lamina cribrosa. METHODS: Frozen sections of the optic nerve head from 7 normal human elderly donors were stained by immunohistochemistry. RESULTS: All six glycoproteins were detected in this tissue. While laminin and entactin/nidogen were observed linearly, reflecting the localization of basement membranes, fibronectin was identified diffusely. Marked tenascin immunoreactivity was apparent in the lamina cribrosa, but little or no tenascin staining was detected in the sclera. Vitronectin showed a fine fibrillar staining pattern in the lamina cribrosa, and, to a lesser extent, in the sclera and pial septa. Thrombospondin staining was apparent only in the sclera and the lamina cribrosa, which traversed the optic nerve. CONCLUSIONS: These results indicate that extracellular matrix components in the lamina cribrosa differ from those in the sclera or pial septa. This study is the first report that the human lamina cribrosa includes vitronectin and thrombospondin.     

Adaptive changes in dynamic properties of human disparity-induced vergence

PURPOSE: Vergence eye movements undergo adaptive recalibration in response to a training stimulus in which the initial disparity is changed just after vergence begins (the double-step paradigm). In the present study the changes in the dynamic properties of convergence, speed and acceleration, were examined by using this double-step paradigm, before and after adaptation. METHODS: Four normal subjects participated. Three-dimensional visual stimuli were provided by a head-mounted display with two liquid crystal diode (LCD) panels. To induce adaptation, a double step of disparity was used: an initial step from distances of 2 to 1 m was followed by a second step to distances of 0.7 m ("increasing paradigm") or 1.4 m ("decreasing paradigm") after a constant period of 0.2 seconds. The dynamic properties of vergence were compared before and after 30 minutes of training with these paradigms. RESULTS: Peak velocity of convergence became significantly greater (increasing paradigm) or smaller (decreasing paradigm) after 30 minutes' training. Changes in the dynamic properties of convergence were also obvious in phase-plane (velocity versus position) and main sequence (peak velocity versus amplitude) plots. Further analysis revealed that adaptive increases in vergence velocity were accomplished by an increase in the duration of the acceleration period, whereas adaptive decreases were induced by a decrease in the maximum value of acceleration. CONCLUSIONS: The pattern of change in the dynamic characteristics of vergence after adaptation was similar to that of saccades and the initiation of pursuit eye movements, suggesting common neural mechanisms for adaptive changes in the open-loop control of eye movements.     

An ultrasound biomicroscopic study of eyes after non-penetrating trabeculectomy

PURPOSES: We studied the control of intraocular pressure(IOP) by various types of blebs after non-penetrating trabeculectomy(NPT) and the difference between bleb formation after penetrating trabeculectomy(PT) and that after NPT. METHODS: The filtering blebs of 45 yeys from 40 patients after NPT were studied using ultrasound biomicroscopy. They were grouped into four types, and the space under the scleral flap was classified into three types. The filtering blebs and the space under the scleral flap were correlated with IOP level. RESULTS: Overall, 40% of the blebs were L(low-reflective) type, 16% H(high-reflective) type, 16% E (encapsulated) type, and 29% F(flattened) type, but in good IOP control cases 59% of the blebs were L type, 14% H type, 14% E type, and 14% F type. L type blebs were found in 94% of eyes with good IOP control. CONCLUSION: Though filtering blebs of the L type could produce sufficient IOP reduction, blebs after NPT showed a greater tendency to become flattened than after PT. Additional systematic therapy must be designed to maintain the L type of filtering blebs after NPT.     

Intraarterial corticosteroid infusion following radiotherapy for primary central nervous system lymphoma: feasibility and preliminary result

To utilize the high lympholytic effect of corticosteroids with minimal systemic adverse effects, we used intraarterial corticosteroid infusion in the treatment of 8 patients with primary central nervous system lymphoma (PCNSL). One patient had recurrent PCNSL, while the other patients had primary disease. Following standard radiotherapy with or without some systemic or intrathecal chemotherapy, prednisolone (60-100 mg in total) or dexamethazone (12 mg in total) was rapidly infused through the carotid arteries in all patients and also through the left vertebral artery in 5 patients. No acute or late complications of this treatment were observed. All 8 patients achieved complete or partial response. Four patients died of the disease, while the other 4 were alive with (1 patient) or without (3 patients) disease at 8-37 months after treatment, giving a 2-year survival rate of 55%. Intraarterial administration of high-dose corticosteroids appears to be a feasible treatment modality. This method may be used in preradiotherapy setting to evaluate response of PCNSL in future studies.